1. Field of Invention
The invention relates to a device for chromatographic separation of a substance mixture, this device being designed as a housing and containing a separation medium in the central partial area. A radial inlet channel for the fluid to be separated is located in the upper partial area of the device and extends to the center of the upper partial area. The housing has an outlet channel in the lower partial area. Separation elements inside the device serve to delineate the upper and lower partial areas from the separation medium. The structural embodiment of the device according to the invention allows a uniform fluid distribution and essentially simultaneous flow-through of the separation medium.
2. Description of the Prior Art
To achieve a good separation performance with chromatographic separation methods, a uniform distribution of the fluid to be separated on the separation medium as well as a simultaneous flow-through of the separation medium are required. The known devices are used in various areas, for example, in the technical, analytical, medicinal and pharmaceutical fields.
Such chromatographic devices comprise a housing or a column, which is usually subdivided into upper, lower and central partial areas. The separation medium, which is usually in the central partial area, may also be referred to as the stationary phase or the adsorbent. The stationary phase usually comprises a solid, a gel or a substance applied to a carrier.
The medium or fluid to be separated, also known as the mobile phase, flows through the separation medium. The substance mixture comprising the mobile phase may be a liquid and/or may be loaded with solids or suspended matter.
In certain types of applications, the upper and/or lower partial areas have a free space delimiting these areas from the separation medium, the so-called stationary phase. Separation elements comprising screens or meshes are often provided to secure the separation medium in the central partial area. These are often equipped with supporting structures and with special fixtures, which should allow an improved fluid characteristic to improve the stability.
The upper and/or lower partial areas may be closed by an upper and/or lower closure device, which may be embodied as an end cap or end cover.
The inlet and/or outlet of the medium to be separated may thus be both axial and radial.
Numerous chromatographic or adsorptive devices are already known from the state of the art.
EP 0 507 245 B1 describes an adsorber housing having a distributor arrangement, which is embodied in the shape of a funnel and tapers conically toward the center of the housing. Rapid and/or complete sedimentation of the separation medium and an improved separation of the solution to be separated are therefore achieved.
US 2001/002581 A1 describes the design of a filter housing, in which a filter is arranged around a cylindrical tube or in a cylindrical tube. The fluid is introduced and discharged radially, with the inlet tube and the outlet tube being situated at the same height. The drawings show that the separated fluid flows through a bell-shaped space forming a gas space upstream from the outlet tube, thereby provided the venting of the filter system.
EP 1 574 244 A2 discloses an end cap for a filter device having a radial inlet or outlet. Guide elements through which the fluid undergoes a reversal of direction are provided in the end cap. The guide elements are arranged in the area of an essentially circular or partially circular channel.
The patent application WO 03/005018 A1 relates to the optimization of fluid distribution systems, in which the fluid distributor structures used for filter systems are fixedly connected to a mesh for retaining the separation medium. Hygienic problems and the formation of dead volumes should be avoided in this way and an improved flow characteristic of the fluid to be separated should be achieved.
DE 10 2008 053 131 A1 describes a method and an arrangement for sterilizing an adsorber housing and the adsorbent, such that the adsorber housing and the adsorbent to be sterilized are kept separately but form a closed system via a connecting device.
Systems having either small-volume housings or complex larger housings, e.g., made of glass, are used in therapeutic immunopheresis.
One disadvantage of these systems is that they are very expensive and are designed as multiuse applications. In addition, these multiuse systems also entail the risk of contamination due to their repeated used on patients and due to the fact that they must be stored in preservative solutions between individual treatments. Dilution effects occur in systems in which the loaded columns are regenerated repeatedly during treatment, and plasma losses. These disadvantages are always especially critical when:                high regeneration cycles are necessary per treatment and/or        larger column volumes are required.        
The columns used with disposable systems are not regenerated within one treatment. There is therefore very little or no risk of plasma dilution and/or plasma losses.
Existing disposable systems such as adsorbers that work with amino acid ligands, for example, are suitable only for certain indications because of their low binding capacity and inadequate selectivity.
Larger column volumes must be used with separation media having a low binding capacity. However, larger volumes can be implemented only with larger diameters of the housings at the same time because otherwise the length of the treatment is increased disproportionately.
Although enlarging the housing diameter allows high plasma volume flow rates, distribution problems occur, resulting in the fact that the fluid to be processed enters the separation medium at different times. In these cases, plasma is entrained and therefore unwanted dilution effects occur. This risk increases especially with a column bed having lateral oncoming flow.
However, if columns having a small diameter are used, it is necessary to run higher plasma flow rates. There is the risk that the binding capacity is reduced because in this case the linear flow rate (cm/min) is increased and too little time is available for the intramolecular interaction of the binding partners. In addition, the risk of an excessively high adsorber pressure or column pressure during the rinsing phase is increased because this is performed at much higher volume flow rates.